The overall objective of the proposed research is to understand how normal tissue cells and cancer cellsmove invasively within organisms - as individual cells, cell clusters and cell sheets. The emphasis is on: A) the mechanism of cell motility within both embryos and adults, particularly during directional morphogenetic movements, how cells make contact with each other and with various substrata over which they move, and how their movements are coordinated; and B) the mechanism of movement of invasive cancer cells, how they make contact with each other, with normal tissue cells, and with various substrata, and how this contact behavior relates to the acquisition of invasiveness. These two lines of emphasis are closely related, in that they are both concerned with properties that make for and influence cell locomotion: adhesiveness of the cell surface and of the substratum, cell to cell junctions and appositions, protrusive activity of the cell surface (especially at the leading edge), detachment and retraction, cell surface flow, endocytosis and exocytosis, cytoplasmic flow and viscosity, microtubules, the organization of actin-containing microfilaments as related to cytoplasmic contractility and tension, contact inhibition and other coordinated interactions between cells moving directionally. The principal techniques that will be utilized are: cell culture, high resolution differential interference contrast and phase contrast optics, interference reflection microscopy, time-lapse cinemicrography and video-filming of cells in vitro and in vivo, planimetry, marking of the cell surface with particles and lectins, transmission, scanning and freeze-fracture electron microscopy, HVEM, micromanipulation and microsurgery, drug inhibition of microtubule assembly, contractility and cell division, TEM of cells treated with electron-dense materials, labeling of contractile proteins with fluorescent antibodies, and introduction of labeled contractile proteins into cells - all in relation to cell motility. When feasible, cells will be studied both in vivo and in vitro and as many of these techniques as apply will be brought to bear in the analysis of each problem.